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Journal of Practical Hepatology

2023 Vol. 26, No. 1 Published:10 January 2023
Hepatitis in vitro, in mice and in rats
Effect of exosomes derived from mesenchymal stem cells on the proliferation and activation of hepatic stellate cells in vitro
Sun Donglei, Guo Jinbo, Wang Dandan, et al
2023, 26(1):  11-14.  doi:10.3969/j.issn.1672-5069.2023.01.004
Abstract ( 121 )   PDF (1696KB) ( 79 )  
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Objective The purpose of this experiment was to investigate the effect of mesenchymal stem cells (MSC)-derived exosomes (MSCs-Exo) on the proliferation and activation of human hepatic stellate cells, e.g. LX-2 cells. Methods The MSCs-Exo were purchased and identified by electron microscopy observation and NanoFCM measurement. The LX-2 cells were stimulated with transforming growth factor-β1 (TGF-β1) at 5 μg/L, 10 μg/L and 20 μg/L concentration, and the α-SMA and COL1A1 mRNA and their proteins were detected by RT-PCR and Western blot. The activated LX-2 cells were intervened by MSCs-Exo at 50 μg/mL, 100 μg/mL at 200 μg/mL for 24 h. The LX-2 cell proliferation was detected by MTT assay. Results The morphological appearance and the particle sizes of MSCs-Exo revealed by transmission electron microscopy and NanoFCM accorded with requirement, and the MSCs-Exo positive marker proteins, CD9 and CD63 were positive, with GM130 protein negative; the α-SMA and COL1A1 mRNA and their protein expression in activated LX-2 cells by TGF-β1 stimulation were significantly increased and positively correlated with TGF-β1 concentration; the α-SMA and COL1A1 mRNA level and their protein expression were highest when the TGF-β1 induction at concentration of 20 μg/L; in the MSCs-Exo-100 and MSCs-Exo-200-intervened activated LX-2 cells, the proliferation viability of cells were significantly reduced compared with in the control (all P<0.0001); the α-SMA and COL1A1 mRNA and their protein expression in TGF-β1-activated LX-2 cells with different concentrations of MSCs-Exo intervention, e.g. at 50 μg/mL, 100 μg/mL and 200 μg/mL, were significantly decreased compared with in the control (P<0.001); the proliferation activities of LX-2 cells intervened by MSCs-Exo-100 and MSCs-Exo-200 were significantly decreased compared to that in the control cells (P<0.0001). Conclusion The MSCs-Exo could inhibit TGF-β1-induced proliferation and activation of LX-2 cells in vitro, and needs further investigation.
Role of E series of prostaglandin receptor 4 on liver fibrosis-related protein expression in mice with carbon tetrachloride-induced liver injuries
Li Rui, Qin Qiushi, Zhang Yue, et al
2023, 26(1):  15-18.  doi:10.3969/j.issn.1672-5069.2023.01.005
Abstract ( 119 )   PDF (1330KB) ( 143 )  
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Objective This experiment aimed at exploring the role of E series of prostaglandin receptor 4 (EP4) on liver fibrosis-related protein expression in mice with CCL4-induced liver injuries. Methods 30 C57BL/6N mice were randomly divided into control, CCL4-intervened, and CCL4 and E7046 conbination-intervened group, with 10 mice in each group. The liver injury model was established by CCL4 intraperitoneal injection, with methylcellulose or EP4-specific antagonist, E7046 solution gavage. After 27 day experiment, the mice were sacrificed under anesthesia, and sera and liver tissues were obtained. The EP4 and α-SMA protein expression and their mRNA levels were detected by Western blot and real-time PCR. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured by automatic biochemical instrument. The liver histopathological examination was performed by HE, Masson and Sirius red staining. Results The hepatic expression of EP4 protein in model mice increased greatly compared to in the control, while it decreased obviously in the combination-intervened mice compared to in the model; similarly, the EP4 encoded Ptger 4 mRNA level in the model group was (3.5±0.1), significantly higher than [(1.0±0.1), P<0.05] in the control, while that was (2.4±0.2) in the combination group, significantly decreased compared to in the model(P<0.05); serum ALT and AST levels in the model were (1753.5±328.6)U/L and (1586.2±204.1)U/L, much higher than in the control(P<0.05), while they decreased greatly in CCL4 and E7046 combination group, e.g., [(885.9±269.6)U/L and (892.4±208.6)U/L, respectively, P<0.05]; the hepatic α-SMA expression in the model was stronger than in the control, while it became obviously weaker in CCL4 and E7046 combination group, and the hepatic Acta2 and Col1a1 mRNA levels in the model up-regulated greatly compared to in the control, and also they became decreased in the CCL4 and E7046-intervened group (P<0.05). Conclusion EP4 might play an pivotal role in CCL4-induced liver fibrosis, which seem to be a target for ameliorating liver fibrosis.
Micro-122 levels in liver fibrosis in vitro and in vivo
Wang Yan, Li Weijia, Li Ya, et al
2023, 26(1):  19-22.  doi:10.3969/j.issn.1672-5069.2023.01.006
Abstract ( 104 )   PDF (1590KB) ( 80 )  
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Objective The purpose of this experiment was to explore the roles of microRNA(miR)-122 in the pathogenesis of liver fibrosis by in vitro and by in vivo. Methods The liver fibrosis model was established in C57BL/6 mice by intraperitoneal injection of carbon tetrachloride and also in HSC-T6 cells in vitro by incubation with 10 ng/ml transforming growth factor-β1 (TGF-β1). The miR-122 agomir and miR-122 mimics were transfected to overexpress miR-122 in mice and in hepatic stellate cells. The total RNA and whole protein were extracted for RT-PCR and Western-blot detection of miR-122, α-smooth muscle actin (α-SMA), type I collagen (Collagen Ⅰ), tissue inhibitor of metalloproteinase 1 (TIMP-1), and platelet-derived growth factor (PDGF). The proliferation of HSC-T6 cells was detected by CCK-8. Results The expression of α-SMA in the liver tissue in the model animal was significantly higher than that in the control group (9.92±2.12 vs. 1.12±0.54, P<0.01), while the miR-122 level was significantly lower than that in the control group (0.95±0.31 vs. 2.07±0.28, P<0.01); in mice with carbon tetrachloride-induced liver fibrosis, the miR-122 level in the miR-122 agomir-transfected group was significantly higher than that in the miR-122 agomir control-transfected group (6.27±1.73 vs. 2.78±0.21, P < 0.01); the α-SMA, type I collagen, TIMP-1 and PDGF protein expression in the miR-122 agomir-transfected group were significantly decreased; in TGF-β1-intervened HST-T6 cells, the α-SMA expression increased as the prolongation of TGF-β1 treatment (0h:0.61±0.02, 12 h:0.69±0.05, 24 h:0.75±0.01, 48 h:1.01±0.03, P<0.05), while the miR-122 levels decreased (0 h:0.72±0.05, 12 h:0.45±0.01, 24 h:0.37±0.03, 48 h:0.29±0.08, P<0.05); the miR-122 level in the miR-122 mimics-transfected cells greatly increased as compared with the miR-122 negative control-transfected cells (178.45±30.62 vs. 12.18±2.39, P<0.01); the Western blot showed that the expression of α-SMA protein was significantly down-regulated in the miR-122 mimics-transfected group; in TGF-β1-intervened HST-T6 cells, the proliferation activity greatly decreased in the miR-122 mimics-transfected group as compared to that in miR-122 negative control-transfected group (P<0.05). Conclusion The miR-122 levels down-regulate in liver fibrosis, and overexpression of it might inhibit the activation and proliferation of hepatic stellate cells, and probably inhibit the occurrence and development of liver fibrosis.
Berberine improves liver injuries and intestinal flora disorders in high-fat diet-induced non-alcoholic fatty liver disease in rats
Huang Danxia, Zhao Zhihui, Xiao Yuexing, et al
2023, 26(1):  23-26.  doi:10.3969/j.issn.1672-5069.2023.01.007
Abstract ( 108 )   PDF (1329KB) ( 65 )  
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Objective The purpose of this experiment was to explore the effect of berberine (BBR) on liver inflammation reaction and intestinal flora changes in rats with non-alcoholic fatty liver disease (NAFLD). Methods Forty-five SD rats were randomly divided into control, model and and BBR-intervened groups, with 15 rats in each group. The NAFLD models were established by high-fat die feeding. The liver pathological changes was observed, and fasting blood glucose (FPG), fasting insulin (FINS) levels and insulin resistance index (IRI) were detected by automatic biochemical analyzer. The fecal 16SrRNA sequence were detected, and serum interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) levels were detected by ELISA. Results At the end of 16 week experiment, the NAFLD model was successfully established as proved in two rats; at the end of the experiment, the liver steatosis and inflammatory reactions improved greatly in BBR-intervened rats as compared to in the model; serum ALT, AST and LDL levels in the BBR-intervened group were (78.0±6.0)IU/L, (119.6±8.8)IU/L and (61.3±5.0)mg/dL, significantly lower than [(211.5±9.0)IU/L, (312.6±9.7)IU/L and (97.6±8.9)mg/dL, respectively, P<0.05], while serum HDL level was (70.0±5.4)mg/dL, significantly higher than [(14.6±5.7)mg/dL, P<0.05] in the model; the FPG, FINS and IRI in BBR-intervened group were (4.1±0.5)mmol/L, (12.7±0.9) mU/L and (2.8±0.4), significantly lower than [(5.9±0.9)mmol/L, (19.3±1.1)mU/L and (4.6±1.0), respectively, P<0.05] in model; the fecal Lachnospira and Clostridium in BBR-intervened group were (5.6±0.5) and (2.0±0.4), significantly lower than[(13.4±1.3) and (7.2±0.6), P<0.05], while the Ruminococci and Lactic acid bacteria were (2.4±0.5 and (2.9±0.5), significantly higher than [(1.0±0.2) and (1.1±0.2), P<0.05] in the model; serum IL-6 and TNF-α levels in BBR-intervened group were (52.1±9.8)pg/mL and (70.0±17.3)pg/mL, both significantly lower than [(80.3±21.6)pg/mL and (120.8±22.6)pg/mL, P<0.05], while serum IL-10 level was (6.1±2.7)pg/mL, significantly higher than [(3.4±1.8)pg/mL, P<0.05] in the model. Conclusion The BBR could alleviate hepatic inflammatory reactions in rats with high-fat diet-induced NAFLD, which might be related to the regulation of intestinal floras.
Viral hepatitis
Comparison of response to recombinant cytokine gene-derived protein or human interferon α-2b and entecavir combination in the treatment of patients with serum HBeAg positive chronic hepatitis B
Zhang Dan, Jiang Jianxin
2023, 26(1):  27-30.  doi:10.3969/j.issn.1672-5069.2023.01.008
Abstract ( 177 )   PDF (831KB) ( 58 )  
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Objective The aim of this study was to compare the antiviral efficacy of recombinant cytokine gene-derived protein (RCGDP) or human interferon α-2b and entecavir combination in the treatment of patients with serum HBeAg positive chronic hepatitis B (CHB). Methods 65 patients with serum HBeAg-positive CHB were recruited in our hospital between March 2019 and March 2021, and were divided into two groups. The interferon α-2b and entecavir combination were given in 33 patients and the RCGDP and entecavir combination were given in 32 patients with CHB. The regimen lasted for 48 weeks in both groups. Serum alanine aminotransferase (ALT) levels, HBV DNA loads and serum HBeAg seroconversion were recorded. Results At the end of 12 week treatment, serum HBeAg negative and HBeAg seroconversion rates in patients receiving entecavir and RCGDP combination were 34.4% and 25.0%, both significantly higher than 9.1% and 6.1% in patients receiving entecavir and interferon α-2b combination therapy (P<0.05); at the end of 48 week treatment, serum ALT normalization, serum HBeAg negative and HBeAg seroconversion rates in patients receiving entecavir and RCGDP combination were 87.5%, 62.5% and 40.6%, all significantly higher than 78.8%, 30.3% and 18.2% in patients receiving entecavir and interferon α-2b combination therapy (P<0.05); during the treatment period, the incidences of fatigue, and fever and headache in entecavir and interferon α-2b combination-treated patients were 21.2% and 84.9%, both significantly higher than 3.1% and 3.1%(P<0.05)in entecavir and RCGDP combination–treated patients, while there were no significant differences as respect to the incidences of neutropenia, thrombocytopenia, decreased appetite, and hypocalcemia between the two groups (P>0.05) . Conclusion The administration of recombinant cytokine gene-derived protein and oral entecavir combination is efficacious in treatment of patients with serum HBeAg positive CHB, with a high HBeAg seroconversion and less untoward effects, as compared with interferon α-2b and entecavir combination therapy, which needs further multi-central clinical investigation.
Non-alcoholic fatty liver diseases
Different activation of peripheral blood invariant natural killer T cells and CD4+/CD8+T cells in patients with nonalcoholic fatty liver diseases
Chen Fenglian, Zhu Qinglan, Zhu Lingli, et al
2023, 26(1):  31-34.  doi:10.3969/j.issn.1672-5069.2023.01.009
Abstract ( 119 )   PDF (938KB) ( 174 )  
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Objective The aim of this study was to investigate the expression of activation markers, such as CD69, CD25, HLA-DR and NKG2D, of peripheral blood invariant natural killer T cells (iNKT), CD4+ and CD8+ T cells in patients with nonalcoholic fatty liver diseases (NAFLD). Methods 64 patients with NAFLD and 50 healthy persons were enrolled in our hospital between January 2020 and July 2022, and all patients with NAFLD received liver biopsies. The expression of activation markers, such as CD69, CD25, HLA-DR and NKG2D in peripheral blood iNKT, CD4+ and CD8+ T cells was detected by FCM. Results The liver histopathological examination showed that the nonalcoholic fatty liver (NAFL) was found in 37 cases and nonalcoholic steatohepatitis (NASH) was found in 27 cases; the percentages of peripheral blood CD69+iNKT cells in healthy individuals, patients with NAFL and patients with NASH were (10.1±1.7)%,(6.1±1.3)% and (26.7±3.6)%(P<0.05), the percentages of CD25+iNKT cells were (83.0±5.9)%, (94.1±8.0)% and (90.8±7.5)%(P<0.05), the percentages of HLA-DR+iNKT cells were (15.3±1.7)%, (15.8±2.0)% and (22.3±2.0)%(P>0.05), and the percentages of NKG2D+iNKT cells were (44.5±3.5)%, (59.7±4.0)% and (71.3±6.0)%(P<0.05); the percentages of peripheral blood CD69+CD4+ T cells were (0.7±0.2)%, (0.4±0.1)% and (0.5±0.1)%(P>0.05), the percentages of CD25+CD4+ T cells were (1.4±0.6)%, (3.0±1.3)% and (1.5±0.7)%(P>0.05), the percentages of HLA-DR+CD4+ T cells were (2.7±0.7)%, (4.1±1.0)% and (3.9±1.0)%(P<0.05), and the percentages of NKG2D+CD4+ T cells were (1.6±0.5)%, (0.6±0.2)% and (0.9±0.2)%(P<0.05); the percentages of peripheral blood CD69+CD8+ T cells in the three groups were (2.0±0.4)%, (1.6±0.3)% and (2.1±0.6)%(P>0.05), the percentages of CD25+CD8+ T cells were (1.3±0.3)%, (1.1±0.2)% and (1.0±0.2)%(P>0.05), the percentages of HLA-DR+CD8+ T cells were (5.0±0.7)%, (6.5±1.0)% and (9.6±1.4)%(P<0.05), and the percentages of NKG2D+CD8+ T cells were (0.6±0.1)%, (0.5±0.1)% and (0.9±0.2)%(P<0.05). Conclusion In this study, we find the immunophenotypic activation differences of peripheral blood iNKT, CD4+ and CD8+ T cells in patients with NAFL and patients with NASH, and the results show that the percentage of CD69+iNK T cells increase in patients with NASH, which might hint the CD69+iNK T cells as a biological marker for the diagnosis of patients with NASH.
Risk factors of non-alcoholic fatty liver diseases in physical examination individuals
Xu Weiqiang, Liu Shuping, Li Xiaomeng
2023, 26(1):  35-38.  doi:10.3969/j.issn.1672-5069.2023.01.010
Abstract ( 125 )   PDF (847KB) ( 347 )  
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Objective The aim of this study was to analyze the risk factors of non-alcoholic fatty liver diseases (NAFLD) in physical examination individuals. Methods 1742 persons received physical examination in our hospital between January 2018 and January 2020, and 485 individuals were eligible for this study based on inclusion and exclusion criteria. The NAFLD was found by ultrasonography in 78 cases and not in 407 cases. The visceral adipose tissue (VAT)was obtained by CT scan, and fasting plasma glucose (FPG) and other common blood parameters were assayed. The risk factors for NAFLD was analyzed by univariate and multivariate Logistic regression. Results The incidences of concomitant blood hypertension, diabetes and hyperlipidemia in patients with NAFLD were 29.5%, 35.9% and 51.3%, much higher than 18.7%, 23.8% and 23.6% (P<0.05), the body mass index, waist and hip circumference were (25.1±1.)kg/m2, (90.4±6.3)cm and (101.3±8.4)cm, much higher than [(22.4±1.1)kg/m2, (81.6±5.7)cm and (95.7±6.2)cm, respectively, P<0.05] in persons without NAFLD; serum TG, LDL-C and VAT were (2.9±0.3)mmol/L,(3.7±0.4)mmol/L and (146.3±12.1)cm2, significantly higher than [(1.6±0.2)mmol/L, (3.1±0.2)mmol/L and (70.5±4.6)cm2, respectively, P<0.05] in persons without NAFLD; serum ALT, FPG and UA levels were (56.6±11.7)u/L, (5.8±0.7)mmol/L and (387.8±36.3)μmol/L, all significantly higher than [(32.4±3.1)u/L, (5.1±0.4)mmol/L and (313.6±51.4)μmol/L, respectively, P<0.05] in persons without NAFLD; the multivariate Logistic regression analysis showed that the increased BMI, elevated VAT, concomitant blood hypertension, and elevated serum TG, LDL-C, ALT and UA levels were all the independent risk factors, while the increased serum HDL-C level was the protective factor for the existence of NAFLD. Conclusion The prevalence of NAFLD in physical examination individuals is relative high, and some increased body health, blood and imaging parameters hints its existence, and warrants further check-up.
Autoimmune liver diseases
Changes of peripheral blood NKp46+ILC3 cells and Th17 cells in patients with autoimmune hepatitis
Wang Haoyu, Zhou Juanyan, Liu Ru, et al
2023, 26(1):  39-42.  doi:10.3969/j.issn.1672-5069.2023.01.011
Abstract ( 142 )   PDF (887KB) ( 117 )  
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Objective The aim of this study was to explore the implications of peripheral blood NKp46+ILC3 cells and Th17 cells in patients with autoimmune hepatitis (AIH). Methods 43 patients with AIH were encountered in our hospital between February 2016 and February 2020. The percentages of peripheral blood NKp46+ILC3 and Th17 positive mononuclear cells were detected by flow cytometry, and the area under receiver operating characteristic (ROC) curve (AUC) was adopted to analyze the efficacy of NKp46+ILC3 cells and Th17 cells in judging the liver histological activity grading in patients with AIH. Results The percentages of NKp46+ILC3 cells and Th17 cells in 10 patients with severe AIH were(0.2±0.2)% and (1.3±0.4)%, significantly lower or higher than [(0.5±0.2)% and (0.8±0.3)%, respectively, P<0.05] in 33 patients with mild to moderate AIH; the percentages of NKp46+ILC3 cells and Th17 cells in 12 AIH patients with liver histological activity G3 to G 4 were(0.3±0.2)% and (1.3±0.4)%, significantly lower or higher than [(0.5±0.2)% and (0.8±0.3)%, respectively, P<0.05] in 31 AIH patients with G1 to G2; the AUC was 0.774(95% CI:0.592-0.957), with the sensitivity (Se) of 75.0% and specificity (Sp) of 87.1% when the peripheral blood NKp46+ILC3 cells ≤0.3% was set as the cut-off-value, and the AUC was 0.853(95% CI:0.734-0.973), with Se of 66.7% and Sp of 90.3% when the peripheral blood Th17 cells >1.1% was set as the cut-off-value in judging severe liver histological activity grading. Conclusion The peripheral blood NKp46+ILC3 cells decrease, and that of Th17 cells increase in patients with AIH, and application of them might help judge the liver histological activity changes.
Drug-induced liver injuries
Changes of serum miR-21 and miR-124a levels in patients with drug-induced liver injury
Lin Shiwen, Han Feng, Wei Yu, et al
2023, 26(1):  43-46.  doi:10.3969/j.issn.1672-5069.2023.01.012
Abstract ( 101 )   PDF (843KB) ( 110 )  
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Objective The aim of this study was to explore the changes of serum microRNA (miR)-21 and miR-124a levels in patients with drug-induced liver injury (DILI) and their clinical implications. Methods 87 patients with DILI and 60 health persons proven by physical examination were enrolled in our hospital between March 2019 and March 2022. Serum miR-21 and miR-124a levels were detected by real-time fluorescence quantitative PCR, and serum nuclear transcription factor-κB (NF-κB) and interleukin-6 (IL-6) levels were determined by ELISA. Results Serum peak ALT, AST, GGT and bilirubin levels in patients with DILI in our series were (143.6±51.8)U/L, (158.2±38.8)U/L, (131.6±26.8)U/L and (41.9±9.6)μmol/L; serum miR-21, miR124a mRNA, NF-κB and IL-6 levels in patients with DILI were (1.4±0.3), (2.6±0.4), (3615.4±526.4)pg/ml and (12.7±1.8)pg/ml, all significantly higher than [(1.0±0.1), (1.1±0.1), (692.2±144.6)pg/ml and (3.4±0.7)pg/ml, respectively, P<0.05] in healthy persons; serum NF-κB and IL-6 levels in patients with mixed DILI were (3874.5±282.5)pg/ml and (14.4±2.6)pg/ml, both much higher than [(3609.8±296.4)pg/ml and (12.6±1.5)pg/ml, respectively, P<0.05] in patients with hepatocyte injury or [(3437.2±253.7)pg/ml and (11.7±1.3)pg/ml, respectively, P<0.05] in DILI patients with cholestasis; unfortunately, there were no significant differences as respect to serum miR-21 and miR-124a levels among patients with different clinical types (P>0.05). Conclusion Serum miR-21 and miR-124a levels in patients with DILI significantly increase as liver function test deteriorated, but their clinical implications is still under investigation.
Benign recurrent intrahepatic cholestasis
Clinical features of patients with benign recurrent intrahepatic cholestasis: a report of three cases
Wang Fu, Wang Haoqi, Zhou Yi, et al
2023, 26(1):  47-50.  doi:10.3969/j.issn.1672-5069.2023.01.013
Abstract ( 760 )   PDF (841KB) ( 103 )  
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Objective The aim of this study was to summarize the clinical features of patients with benign recurrent intrahepatic cholestasis (BRIC). Methods The clinical manifestations, laboratory tests, imaging, pathological examinations, and genetic analysis in three patients with BRIC in Zhongshan Hospital, Fudan University, were retrospectively reviewed. Results The three patients were all male and their initial onset ages were below 20 year old; the common symptoms of the patients were jaundice and pruritus, and two of them also experienced abdominal distension, irregular defecation, and appetite loss; serum total bilirubin, direct bilirubin, ALP and TBA levels increased significantly, while serum GGT, ALT and AST levels stayed normal or increased slightly during the disease attack duration; no abnormal intrahepatic and extrahepatic bile ducts were found in magnetic resonance cholangiopancreatography (MRCP) examination, but obvious cholestasis of hepatocytes and capillary bile duct embolism were observed in liver histopathology; the ATP8B1 gene mutation sites with functional prediction of "potentially harmful" or "likely pathogenic" in pathogenic classification were all detected in three patients; all patients were excluded from other known causes of cholestasis, and the disease was recurrent, but with self-limiting. Conclusion The BRIC is rarely reported and its pathogenesis remains unclear currently. The clinical diagnosis might be made based on clinical manifestations, ancillary tests, and pathological findings after excluding other common causes of liver damage. For patients with high suspicion of BRIC, the genetic tests should be performed as early as possible to clarify the diagnosis and guide the management.
Fitz-Hugh-Curtis syndrome
Clinical feature of patients with Fitz-Hugh-Curtis syndrome
Ni Li, Han Shaowei, Zhou Lishi, et al
2023, 26(1):  51-54.  doi:10.3969/j.issn.1672-5069.2023.01.014
Abstract ( 240 )   PDF (1399KB) ( 136 )  
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Objective The aim of this study was to summarize the clinical features, treatment and prognosis of patients with Fitz-Hugh-Curtis syndrome. Methods The clinical data of 7 patients with Fitz-Hugh-Curtis syndrome in our hospital between January 2016 and April 2021 were retrospectively summarized, including general feature, symptoms and signs, laboratory test results, initial diagnosis, imaging manifestation, gynecological examination, treatment and outcomes. Results All the 7 patients were young women, with the onset of acute abdominal pain; the hepatic capsule enhancement in arterial phase, the uniform enhancement or weakening of liver capsule and liver parenchyma in portal phase and delayed phase were observed in all the 7 cases by abdominal contrast-enhanced CT scan; the acute cholecystitis in 2 cases, acute pancreatitis in 2 cases, and peptic ulcer in 1 case were initially diagnosed before abdominal CT scan; the vaginal secretion examination showed the chlamydia trachomatis in 4 cases; all the 7 patients were treated with ceftriaxone, doxycycline and/or metronidazole combination for two weeks, and all of them recovered. Conclusion In young women at reproductive age with sexual life, the acute onset of persistent epigastric pain or right epigastric pain might hints the Fitz-Hugh-Curtis syndrome, and the diagnosis could be made by gynecological and imaging examination.
Acute fatty liver of pregnancy
Changes of prognosis and causes of death of patients with acute fatty liver of pregnancy in the past two decades
Liu Haixia, Zhu Yunxia, Duan Zhonghui, et al
2023, 26(1):  55-58.  doi:10.3969/j.issn.1672-5069.2023.01.015
Abstract ( 186 )   PDF (840KB) ( 64 )  
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Objective The prognosis of patients with acute fatty liver of pregnancy (AFLP) have dramatically improved, and the main purpose of this study was to summarize the clinical feature shift of the entity in the past two decades. Method The clinical data of patients with AFLP in Beijing You'an Hospital were retrospectively analyzed, and 25 patients in group A were encountered in this hospital between January 2002 and December 2011, and other 28 patients in group B were from January 2012 to January 2022. The clinical manifestations, complications and mortalities in the two groups were compared, and the causes of death were analyzed. Results There was no significant difference respect to serum bilirubin levels in the two groups [(239.8±104.2)μmol/l vs. (161.9±107.7 )μmol/l, P=0.052], while the incidence of abnormal liver function tests in group A was 12.0%, significantly lower than 42.9%(P=0.006) in group B, the cesarean section in group A was 76.0%, much lower than 100.0%(P=0.020) in group B, the incidences of disseminated intravascular coagulation (DIC, 40.0% vs. 3.6%, P=0.001) and the hemorrhagic shock (24.0% vs. 3.6%, P=0.028) were significantly different; the maternal fatality in group B was 3.6%, much lower than 24.0% in group A. Conclusion The leading causes of maternal death in patients with AFLP ten years ago were DIC and massive hemorrhage, while the liver failure is common in recent ten years although the mortality falls dramatically, and the early diagnosis and management is still important.
Hepatic failure
Prevalence of bacterial infection in patients with HBV-related acute-on-chronic liver failure
Wu Chengyong, Chen Chong, Liu Wenyan, et al
2023, 26(1):  59-62.  doi:10.3969/j.issn.1672-5069.2023.01.016
Abstract ( 140 )   PDF (839KB) ( 244 )  
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Objective The purpose of this study was to investigate the prevalence of bacterial infection in patients with hepatitis B viral infection-related acute-on-chronic liver failure (HBV-ACLF). Methods The clinical materials of 214 patients with HBV-ACLF between January 2015 and February 2022 were retrieved from His system in our hospital, and various infections were defined according to related criteria. The multivariate Logistic regression analysis was applied to reveal the impacting factors for infection. Results Out of the 214 patients with HBV-ACLF, the bacteria infection was found in 145 cases(67.7%), involving one organ in 113 cases, two in 28 cases and three in 4 cases, including spontaneous bacterial peritonitis (SBP) in 127 cases (85.2%), pulmonary infection in 41 cases (27.5%), acute cholecystitis in 25 cases(16.8%), urinary tract infection in 4 cases (2.7%) and perianal infection in 2 cases (1.3%); there were significant differences as respect to ages, systemic inflammatory response syndrome (SIRS) score, peripheral white blood cell counts, platelet counts, C-reactive protein, procalcitonin, prothrombin time activity (PTA), serum bilirubin, albumin, the incidence of hepatic encephalopathy (HE) and ascites between patients with and without bacterial infections(P<0.05); the multivariate Logistic analysis showed that the age, SIRS scores, WBC counts, PCT and ascites were the independent risk factors, while the PTA and serum albumin levels were the protective ones for bacterial infection in patients with HBV-ACLF(P<0.05); we set the SIRS score as the basic parameter, and its combination with age in predicting bacterial infection had the sensitivity (Se) and specificity (Sp) of 75.9% and 55.1%, with WBC counts of 77.2% and 62.3%, with PTA of 79.3% and 59.4%, with PCT of 89.7% and 46.4%, with ALB of 80.7% and 63.8%, and with ascites of 67.6% and 72.5%, suggesting a good Se with relatively low Sp. Conclusion The patients with HBV-ACLF are prone to bacterial infection, and some factors, such as elderly persons, hyperbilirubinemia and severe coagulation dysfunction, might trigger the infection, which should be appropriately dealt with as early as possible in clinical practice.
Polarization of peripheral blood macrophages and PBMCs TXNIP/NLRP3 mRNA changes in patients with hepatitis B virus acute-on-chronic liver failure
Shao Simeng, Gao Feng, Jiang Lei, et al
2023, 26(1):  63-66.  doi:10.3969/j.issn.1672-5069.2023.01.017
Abstract ( 130 )   PDF (840KB) ( 57 )  
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Objective The aim of this study was to explore the polarization of peripheral blood macrophages and peripheral blood mononuclear lymphocyte (PBMC) thioredoxin-interacting protein (TXNIP)/nucleotide-binding oligo-merization domain-like receptor protein 3 (NLRP3) mRNA changes in patients with hepatitis B virus acute-on-chronic liver failure (HBV-ACLF). Methods 57 patients with HBV-ACLF and 43 patients with chronic hepatitis B (CHB) were enrolled in our hospital between June 2019 and June 2020, and the percentages of peripheral blood M1 and M2 macrophages were detected by flow cytometry. The PBMC TXNIP, NLRP3 and cysteine protease-1 (caspase-1) mRNA were assayed by real-time fluorescence quantification RT-PCR. Serum interleukin-6 (IL)-6, IL-10 and tumor necrosis factor-α (TNF-α) were detected by ELISA. Results The percentage of M1 macrophages and M1/M2 cell ratio in patients with HBV-ACLF were (3.5±0.4)% and (1.2±0.2), significantly higher than [(2.1±0.2)% and (0.6±0.1), P<0.05], while the percentage of M2 macrophages was (2.5±0.3)%, significantly lower than [(4.1±0.4)%, P<0.05] in patients with CHB; serum IL-6 and TNF-α in patients with HBV-ACLF were (37.9±4.2) ng/L and (2.3±0.2) pg/mL, significantly higher than [(28.8±3.6) ng/L and (1.2±0.1) pg/mL, respectivley, P<0.05], while serum IL-10 level was (1.4±0.2) pg/mL, significantly lower than [(2.9±0.3) pg/mL, P<0.05] in patients with CHB; the PBMCs NLRP3, TXNIP and caspase-1 mRNA in patients with HBV-ACLF were (0.5±0.1), (0.7±0.1) and (1.2±0.1), all significantly lower than [(0.8±0.2), (1.0±0.1) and (1.6±0.2), respectively, P<0.05] in patients with CHB; the percentage of PBMC M1 macrophages in 15 dead patients was (4.1±0.4) %, significantly higher than [(3.3±0.3)%, P<0.05], while the percentage of M2 macrophages, PBMCs NLRP3 and TXNIP mRNA were (1.9±0.2)%, (0.2±0.1) and (0.4±0.1), significantly lower than [(2.7±0.3)%,(0.6±0.1) and (0.8±0.1), respectively, P<0.05] in 42 survivals. Conclusion The peripheral blood macrophages are polarized in the pro-inflammatory direction and the down-regulation of TXNIP and NLRP3 mRNA might be related to immunosuppression in patients with HBV-ACLF.
Combination of NLR and serum IL-6 level in predicting 28-day mortality in patients with acute-on-chronic hepatitis B liver failure
Zhu Xinwen, Wang Weibing, Yuan Fubing, et al
2023, 26(1):  67-70.  doi:10.3969/j.issn.1672-5069.2023.01.018
Abstract ( 110 )   PDF (918KB) ( 84 )  
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Objective The aim of this study was to investigate the predictive performance of short-term prognosis by neutrophil to lymphocyte ratio (NLR) and serum interleukin-6(IL-6) level in patients with acute-on-chronic hepatitis B liver failure (HBV-ACLF). Method 72 patients with HBV-ACLF were encountered in our hospital between September 2019 and September 2021, and were treated by comprehensive conventional supporting therapy. The blood routine was recorded, and serum IL-6 levels were assayed by ELISA. The impacting factors of short-term prognosis were analyzed by multivariate Logistic regression, and the predictive performance of NLR and serum IL-6 levels was evaluated by receiver operating characteristic (ROC) curve. Results The 28-day survival of the 72 patients in our series was 73.6%; the NLR was (7.2±2.2) and serum IL-6 level was (13.6±3.5)pg/ml in 19 dead patients with HBV-ACLF, significantly higher than [(3.7±1.0) and (8.7±1.5)pg/ml, respectively, P<0.05] in 53 survivals, the average age, incidence of hepatic encephalopathy (HE) and model of end stage liver disease (MELD) score in dead patients were significantly greater than, while the platelet count was significantly lower than in survivals (P<0.05); the Logistic regression analysis showed that the age, HE, MELD score, NLR and serum IL-6 levels were all the independent factors impacting the short-term prognosis (P<0.05); the ROC analysis demonstrated that the combination of NLR (>4.93 as the cut-off-value) and serum IL-6 level (>10.9 pg/ml as the cut-off-value) in predicting the 28 day prognosis in patients with HBV-ACLF is promising, with the sensitivity of 100.0% and the specificity of 84.9%. Conclusion The application of NLR and serum IL-6 level combination in predicting the short-term prognosis of patients with HBV-ACLF is efficacious, which needs further clinical investigation.
Liver cirrhosis
Changes of peripheral blood dNLR, MLR and SII in patients with hepatitis B cirrhosis
Xu Haibo, Su Huiting, Xiong Yiping, et al
2023, 26(1):  71-74.  doi:10.3969/j.issn.1672-5069.2023.01.019
Abstract ( 277 )   PDF (845KB) ( 61 )  
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Objective The aim of this study was to explore the clinical implication of peripheral blood derived neutrophil to lymphocyte ratio (dNLR), monocyte to lymphocyte ratio (MLR) and systemic immune inflammatory index (SII) in patients with hepatitis B liver cirrhosis(LC). Methods 85 patients with hepatitis B-induced LC and 85 patients with chronic hepatitis B (CHB) were encountered in our hospital between January 2019 and December 2021. Serum tumor necrosis factor -α(TNF-α), interleukin-6 (IL-6) and IL-17 levels were detected by ELISA. The peripheral blood platelet, lymphocyte, neutrophil and monocyte counts were detected by full-automatic blood cell analyzer. Results Serum bilirubin level and INR in patients with LC were(43.1±8.5)μmol/L and (1.3±0.6), much higher than [(19.4±3.0)μmol/L and (1.1±0.2), P<0.05], while serum ALT and albumin levels were (63.6±8.2)U/L and (30.8±4.6)g/L, much lower than [(104.1±14.9)U/L and (39.0±8.1)g/L, respectively, P<0.05] in patients with CHB; serum TNF-α, IL-6 and IL-17 levels in patients with LC were (88.7±11.6)pg/mL, (95.6±12.5)pg/mL and (45.6±8.9)ng/mL, significantly higher than [(68.2±9.3)pg/mL, (67.9±9.5)pg/mL and (25.5±5.1)ng/mL, respectively, P<0.05] in patients with CHB; the dNLR, MLR and SII in patients with (2.2±0.5), 0.8(0.7, 0.9) and (553.9±83.4), significantly higher than [(1.8±0.3), 0.6(0.5, 0.7) and (481.4±99.3), P<0.05] in patients with CHB; the dNLR, MLR and SII in LC patients with Child class B/C were significantly higher than in those with Child class A(P<0.05), and the dNLR, MLR and SII in patients with Child class C were significantly higher than in patients with Child class B (P<0.05). Conclusion The peripheral blood dNLR, MLR and SII significantly increase in patients with hepatitis B cirrhosis, and their changes are related to disease severity.
Observation of ornithine aspartate at base of colon dialysis in treatment of patients with hepatic encephalopathy
Li Susu, Dong Yuan, Jia Haoyan, et al
2023, 26(1):  75-78.  doi:10.3969/j.issn.1672-5069.2023.01.020
Abstract ( 142 )   PDF (841KB) ( 230 )  
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Objective The aim of this study was to observe the short-term efficacy of ornithine aspartate at base of colon dialysis in treatment of patients with hepatic encephalopathy (HE). Methods 123 patients with liver cirrhosis and complicated HE were encountered in our hospital between January 2019 and December 2021, and were randomly divided into control (n=61)and observation group (n=62), receiving colon dialysis or colon dialysis and intravenous ornithine aspartate administration at base of conventional supporting treatment for 7 to 10 days. Serum tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), IL-6, plasma β-endorphin (β-EP) and endotoxin (LPS) were detected by ELISA. The blood ammonia was routinely detected. The cognitive function was assessed by mini-mental state examination (MMSE) and by number connection test (NCT). Results At the end of the treatment, the mortality rate in the observation group was significantly lower than that in the control group (16.1% vs. 36.1%, P<0.05); the total serum bilirubin level in the observation group was (41.6±8.2) μmol/L, significantly lower than [(50.8±9.4) μmol/L, P<0.05] in control group, and blood ammonia level was (60.8±6.3) μmol/L, significantly lower than [(82.4±9.6) μmol/L, P<0.05] in the control group; serum TNF-α, IL-8, IL-6, β-EP and LPS levels in the observation group were (27.5±5.3)ng/L, (44.9±7.2)ng/L, (50.6±8.4)ng/L, (38.6±3.8)pg/mL and (17.5±3.1)pg/mL, all significantly lower than [(39.7±6.8) ng/L, (62.8±9.3)ng/L, (74.8±11.5)ng/L, (50.7±4.9)pg/mL and (24.8±3.6)pg/mL, respectively, P<0.05] in the control; the MMSE score was (27.4±3.8), much higher than [(23.9±3.6), P<0.05], while the time of NCT was (50.3±4.8) s, much quicker than [(60.5±5.9)s, P<0.05] in the control group. Conclusion The intravenous infusion of ornithine aspartate at base of colon dialysis in the treatment of patients with HE could improve the short-term survival, which might be related to the reduction of blood ammonia andβ-EP levels as well as the inhibition of inflammatory reaction.
Cardiac structural and functional changes in patients with hepatitis B cirrhosis after undergoing transjugular intrahepatic portosystemic shunt
Chen Ye, Chen Xiaolan, Cao Liling, et al
2023, 26(1):  79-82.  doi:10.3969/j.issn.1672-5069.2023.01.021
Abstract ( 219 )   PDF (1007KB) ( 121 )  
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Objective The aim of this study was to explore the cardiac structural and functional changes in patients with hepatitis B cirrhosis after undergoing transjugular intrahepatic portosystemic shunt (TIPS). Methods 48 patients with hepatitis B-induced liver cirrhosis (LC) were encountered in our hospital between January 2018 and June 2021, and all underwent TIPS. The cardiac structural and functional parameters, including indexed right atrial volume (RAVI), indexed right ventricular end-diastolic volume (RVEDVI), indexed right ventricular end-systolic volume (RVESVI), indexed right ventricular stroke volume (RVSVI), right ventricular ejection fraction (RVEF), indexed left atrial volume (LAVI), indexed left ventricular end-diastolic volume (LVEDVI), indexed left ventricular end-systolic volume (LVESVI), indexed left ventricular stroke volume (LVSVI), left ventricular ejection fraction (LVEF) and indexed left ventricular myocardial mass (LVEDMI) were detected by cardiovascular magnetic resonance imaging (CMR). The RA area, tricuspid annular plane systolic excursion (TAPSE), LAVI, LVEF and ratio of E/e' were detected by echocardiography. Results At the end of six months after TIPS, the RAVI, RVEDVI, RVESVI, RVSVI, LAVI, LVEDVI, LVESVI, LVSVI and LVEDMI changed greatly as compared to before TIPS in the 48 patients with LC (P<0.05); the RA area, LAVI and ration E/e' echocardiography six months after TIPS were 18(15, 24)cm2, 32(28, 45)ml/m2 and 11(8,16), significantly different as compared to 16(12,19)cm2, 23(20, 27)ml/m2 and 8(5, 10)at presentation(P<0.05). Conclusion The heart volume increases and eccentric left ventricular hypertrophy occurs after TIPS in patients with LC, and their impact on cardiac functions needs further investigation.
Diagnostic performance of simplified animal nomenclature test in predicting minimal hepatic encephalopathy in patients with liver cirrhosis
Liu Nannan, Li Wei, Zhao Shousong
2023, 26(1):  83-86.  doi:10.3969/j.issn.1672-5069.2023.01.022
Abstract ( 147 )   PDF (919KB) ( 72 )  
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Objective The aim of this study was to investigate the diagnostic performance of simplified animal nomenclature test (S-ANT) in predicting minimal hepatic encephalopathy (MHE) in patients with liver cirrhosis (LC). Methods 142 patients with LC were encountered in the Department of Infectious Diseases, First Affiliated Hospital, Bengbu Medical College and the Department of Hepatology, Second People's Hospital, Fuyang, Anhui province between July 2020 and June 2021, and the number connection test-A (NCT-A), digit symbol test(DST), simplified animal naming test(ANT) were conducted for the diagnosis of MHE. The multivariate Logistic regression analysis was performed, the receiver operating characteristic (ROC) curve was drawn, and the area under the curve (AUC) was calculated to evaluate the diagnostic performance of S-ANT for MHE. Results Among the 142 patients with LC, the MHE was found in 39 cases (27.5%); there were significant differences with respect to the ages, education periods and the percentage of alcoholic liver disease between patients with and without MHE(P<0.05);serum ammonia level in patients with MHE was 61.0(36.0, 94.0)μmol/L, much higher than [(47.1(33.0, 69.0)μmol/L, P<0.05] in patients without MHE; the NCT-A in patients with MHE lasted for (93.5±38.9)s, much longer than [(61.5±23.7)s, P<0.05], and the DST, ANT and S-ANT scores were (22.7±5.7), (12.5±1.5) and (14.4±2.0), all significantly higher than [(36.9±10.4), (17.6±3.9) and (18.7±3.8), respectively, P<0.05] in patients without MHE; the multivariate Logistic regression analysis showed that the age(OR=1.07, 95%CI 1.02-1.14, P<0.05), education period (OR=0.78, 95%CI 0.65-0.94, P<0.05) and serum ammonia level (OR=1.02, 95%CI 1.00-1.04, P<0.05) were all the independent factors for the occurrence of MHE; the AUC was 0.781, with the sensitivity of 71.8% and the specificity of 84.5%, when the cut-off-value of S-ANT less than 16 was applied to predict the MHE in patients with LC. Conclusion The S-ANT is a good diagnostic tool for the assessment of MHE in patients with LC, which might be applied to screen and early find the suspicious patients.
Efficacy of endoscopic ligation and tissue glue injection in the treatment of patients with hepatitis B liver cirrhosis and esophageal and gastric varices bleeding
Dai Huan, Li Kai, Zhu Yongxiang, et al
2023, 26(1):  87-90.  doi:10.3969/j.issn.1672-5069.2023.01.023
Abstract ( 160 )   PDF (837KB) ( 166 )  
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Objective The aim of this study was to investigate the efficacy of endoscopic varices ligation (EVL) and tissue glue injection (TGI) in the treatment of patients with hepatitis B liver cirrhosis (LC) and esophageal and gastric varices bleeding (EVB). Methods 80 patients with LC and EVB were encountered in our hospital between February 2016 and January 2021, and all were carefully managed by conventional hemostasis measures. 40 patients in the control taken propranolol orally after hemostasis, and another 40 patients in the observation group received EVL and TGI. All patients were followed-up for six months. The portal venous diameter (DPV), portal venous blood velocity (VPV) and blood quantities of portal vein (QPV) were detected by ultrasonography. Serum gastrin (GAS), motilin (MTL), lipid peroxide (LPO) and malondialdehyde (MDA) levels were assayed by ELISA. Results The amount of blood transfusion, hemostatic time and hospital stay in the observation group were (3.2±0.6) u,(23.8±5.1)h and (7.5±1.3)d, significantly less or shorter than [(5.0±0.9) u, (47.9±7.5)h and (12.1±1.5)d, respectively, P<0.05] in the control; after treatment, the VPV and QPV in the observation were (18.7±2.3)cm/s and (510.2±52.2) ml/min, both significantly lower than [(22.2±2.4)cm/s and (645.2±64.1)ml/min, respectively, P<0.05] in the control; serum GAS, MTL, LPO and MDA levels in the observation were (98.2±9.1)μg/ml, (219.5±20.2)ng/l, (5.1±1.5)U/l and (13.6±3.4)μmol/l, all significantly lower [(112.4±11.7)μg/ml,(251.2±20.4)ng/l,(15.2±6.8)U/l and (22.1±5.3)μmol/l, respectively, P<0.05]; at the end of six-month follow-up, the incidences of re-bleeding and fatality in the observation were 15.0% and 5.0%, both significantly lower than 40.0% and 30.0%(P<0.05) in the control group. Conclusion The EVL and TGI in the treatment of hepatitis B cirrhotics with complicated EVB is efficacious with a promising hemostatic effect and elevated survival, which warrants further clinical investigation.
Imaging and histopathological features in patients with idiopathic non-cirrhotic portal hypertension
Xu Qing, Yang Jian, Zong Jinjuan
2023, 26(1):  91-94.  doi:10.3969/j.issn.1672-5069.2023.01.024
Abstract ( 105 )   PDF (2213KB) ( 92 )  
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Objective The aim of this study was to summarize the imaging and liver histopathological features in patients with idiopathic non-cirrhotic portal hypertension (INCPH) and to find the differential clue from patients with liver cirrhosis (LC). Methods Sixteen patients with INCPH and twenty-eight patients with hepatitis B-induced LC were encountered in our hospital between January 2016 and July 2021, and all underwent ultrasonography, CT, MR and liver biopsies. Results The imaging check-up showed that there were significant differences as respect to liver diffuse nodular changes (0.0% vs. 35.7%), portal vain diameters [9.7(7.2, 11.6)mm vs. 13.6(9.2, 15.7)mm], and portal vain wall thickness [2.6(1.4, 4.0)mm vs. 1.4(1.1, 1.6)mm] between the two groups(P<0.05); the liver histopathological examination demonstrated that there were significant differences respect to portal vein region fibrosis, hepatic diaphragm fibrosis, hepatic interlobular vein occlusion, hepatocyte necrosis or edema and hepatocyte steatosis [100.0% vs. 0.0%, 18.7% vs. 92.8%, 56.2% vs. 10.7%, 0.0% vs. 75.0% and 12.5% vs. 89.3%] between the two groups (P<0.05). Conclusion INCPH is still a disease of unknown etiology. The liver imaging and histopathological features might help differentiate it from liver cirrhosis.
Hepatoma
Pathogenesis of hepatocellular carcinoma associated with CDC20 expression
Zou Chunyan, He Yanpeng, Chai Xiukun, et al
2023, 26(1):  95-99.  doi:10.3969/j.issn.1672-5069.2023.01.025
Abstract ( 122 )   PDF (1377KB) ( 231 )  
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Objective Hepatocellular carcinoma (HCC) is one of the most common liver malignancies in the world. The etiology and molecular events HCC are still unclear. We tried to identify the key pathogenic gene, the cell division cycle 20 (CDC20) by comprehensive bioinformatics, which was related to the pathogenesis of HCC with certain underlying molecular mechanism. Methods We downloaded GSE36376 gene expression profile from Gene Expression Omnibus (GEO) database, found 433 samples, of which 240 HCC tissues and 193 of normal liver tissues, and were analyzed by comprehensive bioinformatics. The R software in RStudio was applied to screen the differential gene expression (DEG) in HCC and normal liver tissues, and the protein-protein interaction (PPI) network of DEG was constructed from the STRING database. The Metascape online tool was applied to carry out enrichment analysis, at the same time, the MCODE was used to identify Hub gene. Results The GSE36376 data was screened to get 706 DEGs, among them, a total of 554 down-regulated genes and 152 up-regulated genes were identified; the significant up-regulated genes were UBE2C, CDC20, COL4A1, NUSAP1, HSP90AB1, and CDKN3 from the PPI network; the Metascape enrichment analysis showed that in the GO biological process, it was mainly concentrated in the small molecule catabolism, the monocarboxylic acid metabolism, the steroid metabolism, the cofactor metabolism, the drug catabolism, the primary alcohol metabolism, and the effects of toxic substances; it also involved the organic anion transport, monosaccharide metabolism, aromatic amino acid family metabolism, detoxification, primary alcohol catabolism, and organic cyclic compound catabolism, etc; as for the KEGG signal pathway, it was mainly focused on carbon metabolism, fatty acid degradation, complement and coagulation cascade, tryptophan metabolism and peroxisomes, etc; the Hub genes were UBE2C, CDC20 and HSP90AB1 from MCODE. Conclusion The CDC20 gene obtained by comprehensive bioinformatics is a key gene for pathogenesis of HCC, which might be important for early diagnosis and therapeutic target.
Performance of quantitative parameters by dynamic contrast-enhanced magnetic resonance imaging in the diagnosis of benign and malignant hepatic space-occupying lesions
Jiang Huizhen, Chen Jun, Chen Chunmei, et al
2023, 26(1):  100-103.  doi:10.3969/j.issn.1672-5069.2023.01.026
Abstract ( 203 )   PDF (1250KB) ( 56 )  
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Objective The aim of this study was to explore the performance of quantitative parameters by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the diagnosis of benign and malignant hepatic space-occupying lesions. Methods A total of 88 patients with hepatic space-occupying lesions confirmed by histopathological examination after surgery or fine needle aspiration biopsy were encountered in our hospital between February 2019 and February 2022. The histopathological results showed that there were 47 patients with benign hepatic lesions and 41 patients with liver cancer. All patients underwent DCE-MRI scanning to measure the mean enhancement time (MET), positive enhancement integral (PEI), maximum slope of increase (MSI) and maximum slope of decrease (MSD). The liver tissue Cripto-1, Kruppel-like factor (KLF4), homolobox A9(HOXA9) and transmembrane protein 3(IFITM3) mRNA levels were detected by fluorescence quantitative polymerase chain reaction (PCR). The diagnostic efficacy of parameter was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC). Results The MET, PEI and MSI in the malignant lesions were (516.5±40.2)s,(32.4±6.3) and (99.6±17.8), all significantly lower than [(574.3±50.9)s,(256.7±22.7) and (271.6±25.3), respectively, P<0.05], while the MSD was (114.6±14.2), significantly higher than [(85.4±10.9), P<0.05] in the benign lesions; the Cripto-1 and IFITM3 mRNA levels in the malignant lesions were (130.3±17.5) and (141.8±19.2), both significantly higher than [(101.5±14.2) and (103.5±13.6), respectively, P<0.05], while the KLF4 and HOXA9 mRNA levels were (70.4±8.6) and (65.7±6.9), both significantly lower than [(99.8±12.6) and (98.8±11.4), respectively, P<0.05] in benign lesions; the ROC analysis showed that the AUC was 0.900, with the sensitivity of 96.0%, and the specificity of 80.0%, when the MET, PEI, MSI and MSD combination (equal to or greater than 534.7 s, 77.9, 136.8 and 100.5, respectivyly, as the cut-off-value) in predicting intrahepatic malignant lesions, superior to any parameter of them (P<0.05). Conclusion The quantitative parameters obtained by DCE-MRI scan are helpful for differential diagnosis of benign and malignant hepatic space-occupying lesions, which warrants further investigation.
Differential diagnosis of hepatic hemangioma and hepatocellular carcinoma by multi-b-value diffusion-weighted imaging of high-field magnetic resonance
Gao Xiangrui, Liu Hongyan, Zhang Huai, et al
2023, 26(1):  104-107.  doi:10.3969/j.issn.1672-5069.2023.01.027
Abstract ( 176 )   PDF (1391KB) ( 61 )  
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Objective The aim of this study was to investigate the differential diagnosis of hepatic hemangioma (HH) and hepatocellular carcinoma (HCC) by multi-b-value diffusion-weighted imaging (DWI) of high-field magnetic resonance (MR). Methods 85 patients with focal space-occupying liver lesions (FLL) were encountered in our hospital between June 2019 and May 2021, and all underwent high-field magnetic resonance and the apparent diffusion coefficient (ADC) was recorded. All patients received hepatectomy, and the histopathological examination was performed. The receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) was calculated to testify the differential diagnosis performance of ADC value for HH and HCC. Results The results of pathological examination post-operationally showed that among the 85 patients with FLL, the HH was found in 28 cases (32.9%), the focal liver nodular hyperplasia (FNH) was found in 18 cases (21.2%) and the HCC was found in 39 cases (45.9%); the ADC of cancerous foci at b=50 s/mm2, b=400 s/mm2 and b=1000 s/mm2 were (2.41±0.20)×10-3/mm2/s, (2.02±0.19)×10-3/mm2/s and (1.73±0.15)×10-3/mm2/s, the ADC of FNH foci were (2.43±0.31)×10-3/mm2/s, (2.05±0.21)×10-3/mm2/s and (2.01±0.18)×10-3/mm2/s, all significantly lower than [(2.63±0.35)×10-3/mm2/s, (2.46±0.32)×10-3/mm2/s and (2.25±0.23)×10-3/mm2/s, respectively, P<0.05] in HH foci; the ROC was drawn based on ADC at b=1000 s/mm2, and the ADC=1.73×10-3/mm2/s was set as the optimal cut-off-value for differential diagnostic of HH and HCC, the performance is excellent with the AUC(95%CI) of 0.727(0.581-0.844, P<0.05), the sensitivity of 80.0% and the specificity of 75.9%. Conclusion The high-field magnetic resonance imaging has a great importance in the differential diagnosis of hepatic hemangioma and hepatocellular carcinoma, and we recommend the ADCs at b equal to 1000s/mm2, which needs further clinical investigation.
TACE with sequential microwave ablation followed by oral sorafenib maintenance in treatment of patients with large hepatocellular carcinoma
Ding Haibin, Zhang Xin, Li Ya, et al
2023, 26(1):  108-111.  doi:10.3969/j.issn.1672-5069.2023.01.028
Abstract ( 111 )   PDF (839KB) ( 83 )  
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Objective The purpose of this study was to investigate the clinical efficacy of transhepatic arterial chemoembolization (TACE) with sequential microwave ablation (MWA) followed by oral sorafenib maintenance in treatment of patients with large hepatocellular carcinoma (HCC). Methods A total of 144 patients with large HCC were encountered in our hospital between April 2017 and April 2019, and 74 patients were treated by TACE with sequential MWA followed by oral sorafenib maintenance and another 70 patients received TACE and oral sorafenib. All patients were followed-up for two years. Results At the end of three month, the objective remission rate and disease control rate in the combination group were 73.0% and 98.6%, both significantly higher than 47.1% and 88.6%(P<0.05) in TACE-treated patients; serum AFP level was (128.0±14.4)μg/L, significantly lower than [(208.7±27.3)μg/L, P<0.05], and KPS's score was (88.7±8.2), significantly higher than [(79.4±7.9), P<0.05] in TACE-treated patients; the incidence of post-operational complications was 39.2%, not significantly different compared to 34.3% in TACE-treated patients (P>0.05); the incidence of diarrhea, anorexia, alopecia, nausea and vomiting, and skin reactions were 24.3%, 27.0%, 20.3%, 13.5% and 18.9%, not significantly different compared to 24.3%, 30.0%, 24.3%, 17.1% and 18.6% in TACE-treated patients (P>0.05); at the end of two-year followed-up, 5 cases and 2 cases were lost in the two groups respectively, and the one-year survival rate in the combination group was 97.1%(67/69) and the two-year survival rate was 73.9%(51/69), both significantly higher than 79.4%(54/68) and 52.9%(36/68) in TACE-treated patients (Log-Rank=11.857, P=0.001). Conclusion The strategy of TACE with sequential MWA and oral sorafenib maintenance in treating patients with large-volume HCC is encouraging, which warrants further clinical investigation.
Clinical efficacy of PD-1 inhibitor and lenvatinib in the treatment of elderly patients with advanced primary liver cancer
Peng Yu, Li Haitao, Yang Wenli, et al
2023, 26(1):  112-115.  doi:10.3969/j.issn.1672-5069.2023.01.029
Abstract ( 639 )   PDF (913KB) ( 147 )  
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Objective The aim of this study was to explore the clinical efficacy of programmed cell death protein-1 (PD-1) inhibitor and lenvatinib in the treatment of elderly patients with advanced primary liver(PLC). Methods 56 patients with advanced PLC were admitted to our hospital between February, 2017 and February, 2020, and were divided into control (n=28) and observation group (n=28), receiving lenvatinib or PD-1 inhibitor, tirelizhu, and lenvatinib combination therapy. The peripheral blood lymphocyte subsets, CD4+ cell surface PD-1 and cytotoxic T-lymphocyte antigen 4 (CTLA-4) were detected by FCA. Serum acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels were detected by ELISA. Results At the end of three month treatment, there were no significant differences as respect to the objective remission rate (42.9% vs. 25.0%) and local control rate(78.6% vs. 64.3%, P>0.05); the percentages of CD3+, CD4+ and CD8+ cells in the combination treatment group were much higher than, while the CD4+/CD8+ cell ratio, as well as the cell PD-1 and CTLA-4 expression were much lower than in the control (P<0.05); serum aFGF, bFGF and VEGF levels in the observation group were (4.1±0.8)pg/L, (5.1±1.0)pg/L and (13.5±2.7)ng/ml, all significantly lower than [(5.3±0.9)pg/L, (6.1±0.8)pg/L and (18.6±3.1)ng/ml, respectively, P<0.05] in the control; at the end of two-year follow-up, there was no significant difference respect to the progression free survival (10.7% vs. 21.4%, P>0.05) between the two groups, while the overall survival in the observation group was 60.7%, much higher than 25.0% (P<0.05) in the control. Conclusion The strategy of PD-1 inhibitor and lenvatinib combination in the treatment of elderly patients with advanced PLC could improve immune functions and prognosis, which needs further investigation.
Clinical observation of camrelizumab therapy after TACE in the treatment of patients with advanced primary liver cancer
Du Shangyun, Weng Li, Wu Min
2023, 26(1):  116-119.  doi:10.3969/j.issn.1672-5069.2023.01.030
Abstract ( 137 )   PDF (861KB) ( 85 )  
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Objective The aim of this study was to observe the clinical efficacy of camrelizumab therapy after transhepatic arterial chemoembolization (TACE) in the treatment of patients with advanced primary liver cancer (PLC). Methods A total of 116 patients with advanced PLC were admitted to Suzhou First People's Hospital between March 2018 and March 2021, and randomly divided into control and observation group, with 58 patients in each group. The patients in the control group were treated with TACE, and those in the observation group were treated with TACE and after that the carrierizumab was given for six months to one year. Serum alpha fetoprotein (AFP), alpha fetoprotein heterogeneity-L3 (AFP - L3) and carcinoembryonic antigen (CEA) levels were detected by ELISA. The peripheral blood T lymphocyte subsets were determined by FCM. The survival curve was drawn by Kaplan-Meier and compared by Log-Rank test. Results At the end of three month treatment, the complete remission, partial remission, stable disease, objective remission rate and disease control rate in the observation group were 8.6%, 48.3%, 29.3%, 56.9% and 86.2%, much superior to 1.7%, 36.2%, 31.0%, 37.9%(P<0.05) and 69.0%(P<0.05) in the control group; serum AFP, AFP - L3 and CEA were(86.5±28.7)ng/mL, (183.7±61.4)ng/mL and (9.1±2.6)ng/mL, significantly lower than [(185.8±34.9)ng/mL, 270.3±71.5)ng/mL and (25.4±3.6)ng/mL, respectively, P<0.05] in the control; the percentage of peripheral blood CD4 cells and the CD4/CD8 cell ratio were (38.6±4.1)% and (1.3±0.2), both significantly higher than [(32.3±3.7)% and (1.1±0.1), respectively, P<0.05] in the control; up to the end of two-year follow-up, the survival rate in the observation group with two missed was 64.3%(36/56), much higher than 43.9%(25/57, x2=3.618, P=0.045) in the control with one missed. Conclusion We recommend the carlizumab therapy after TACE in the treatment of patients with advanced PLC, which needs further clinical investigation.
Comparison of laparoscopic hepatectomy and open hepatectomy in the treatment of patients with intrahepatic cholangiocarcinoma
Dong Xianjin, Su Wei, Li Liansheng, et al
2023, 26(1):  120-123.  doi:10.3969/j.issn.1672-5069.2023.01.031
Abstract ( 95 )   PDF (840KB) ( 67 )  
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Objective The aim of this study was to compare the clinical efficacy of laparoscopic hepatectomy (LH) and open hepatectomy (OH) in the treatment of patients with intrahepatic cholangiocarcinoma (ICC). Methods 122 patients with ICC were enrolled in our hospital between February 2018 and February 2021, and were divided into control (n=61) and observation group (n=61), underwent OH or LH. All patients with ICC were followed-up for half a year. Serum C-reactive protein (CRP), cortisol (Cor) and interleukin-6 (IL-6) levels were detected by ELISA. Results The operation time, the intraoperative blood loss, the postoperative first anal exhaust time and the postoperative hospitalization time in patients receiving LH were (232.2±50.4)min, (592.3±164.7)ml, (2.1±0.8)d and (6.5±1.3)d, significantly shorter or less than [(321.1±69.7)min, (995.5±321.4) ml, (2.7±0.7)d and (8.2±1.7)d, respectively, P<0.0 5] in patients receiving OH; at the end of 3 days after operation, serum CRP, Cor and IL-6 levels in patients receiving LH were (25.1±4.0)mg/L,(529.6±75.4)mmol/L and (83.5±7.2)pg/ml, all significantly lower than [(39.8±5.1)mg/L, (654.7±78.1) mmol/L and (97.3±10.2)pg/ml, respectively, P<0.05] in patients receiving OH; at 7 days, serum AST level in patients with LH operation was (155.2±12.7)U/L, much lower than [(209.3±17.0)U/L, P<0.05] in patients with OH operation; at 30 days, the incidence of untoward effects in patient with LH operation was 11.5%, much lower than 26.2%(P<0.05) in patients with OH operation; at the end of six month follow-up, there were no significant differences respect to the tumor recurrence and the mortality rates between the two groups (3.3% and 3.3% vs. 1.6% and 4.9%, respectively, P>0.05). Conclusion The LH is a reasonable choice for patients with ICC, with a relative rapid recovery, which might be related to the mild inflammatory reactions.
Cholelithiasis
Clinical efficacy of laparoscopic hepatectomy in the treatment of patients with intrahepatic bile duct stones
Yin Qiushi, Wang Xueguo, Song Qifeng
2023, 26(1):  124-127.  doi:10.3969/j.issn.1672-5069.2023.01.032
Abstract ( 101 )   PDF (832KB) ( 75 )  
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Objective The aim of this study was to compare the clinical efficacy of first laparoscopic hepatectomy (LH) and thereafter common bile duct incision for stone removal, or vice versa in the treatment of patients with intrahepatic bile duct stones (IHBDS). Methods 90 patients with IHBDS were enrolled in our hospital between January 2017 and October 2021, and the 53 patients in group A received first LH and thereafter common bile duct incision for stone removal and 37 patients in group B received first common bile duct incision for stone removal and thereafter LH. All patients were followed-up for six months. Results The surgical time, postoperative drainage tube removal and postoperative hospital stay in group A were(226.1±45.3)min, (7.1±1.8)d and (8.0±1.5)d, all significantly shorter than [(294.5±58.8)min, (8.4±2.0)d and (9.7±2.4)d, respectively, P<0.05], and intraoperative blood loss was (215.4±39.7)ml, also significantly less than [(328.2±37.2)ml, P<0.05] in group B; there were no significant differences as respect to blood biochemical parameters between the two groups at presentation and 5 days after operation(P>0.05); at the end of three month follow-up, the incidences of post-operational complications, such as incision infection, ascites, bile leakage, biliary bleeding and cholangitis between the two groups were not significantly different(13.2% vs. 24.3%, P>0.05); at the end of six month follow-up, the stone recurrence rates were not statistically significant between the two groups (5.7% vs 8.1%, P>0.05). Conclusion The first LH and thereafter common bile duct incision for stone removal, or vice versa in the treatment of patients with IHBDS could not lead to a different outcomes of patients, and the surgeons might make the decisions based the patients' conditions. We vigorously recommend them to summarize the clinical experiences to give out the indications.
Efficacy of primary suture laparoscopic common bile duct exploration in the treatment of patients with choledocholithiasis
Zhang Fu, Chen Junmao, Liang Xiaohui
2023, 26(1):  128-131.  doi:10.3969/j.issn.1672-5069.2023.01.033
Abstract ( 242 )   PDF (835KB) ( 121 )  
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Objective The aim of this study was to investigate the clinical efficacy of primary suture laparoscopic common bile duct exploration (LCBDE) in the treatment of patients with choledocholithiasis. Methods 74 patients with choledocholithiasis were encountered in our hospital between January 2018 and October 2021, and among them, 31 patients in control group were treated with T-tube drainage after LCBDE and another 43 patients in observation group were treated with primary suture LCBDE. All patients were followed-up for 6 months after operation. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB) and total bilirubin (TBIL) levels were detected by using an automatic biochemical analyzer, and serum stress response indicators, such as adrenaline (A), adrenocorticotropic hormone (ACTH) and cortisol (COR) levels were assayed by radioimmunoassay. Results The operation time, intraperitoneal drainage time and hospital stay in the observation group were(91.3±12.6)min, (3.3±1.2)d and (5.9±1.2)d, significantly shorter than [(115.4±19.2)min, (4.5±1.4)d and (8.6±1.5)d, respectively, P<0.05] in the control; there were no significant differences as respect to serum biochemical parameters between the two groups(P>0.05); 3 days after operation, serum A, ACTH and COR levels in the observation were (1.2±0.3) nmol/L,(13.6±4.1)ng/mL and (212.9±21.4)ng/mL, all significantly lower than [(1.6±0.4)nmol/L, (17.2±4.8)ng/mL and (256.4±35.7)ng/mL, P<0.05] in the control; at the end of six month follow-up, the post-operational complications in the observation was 9.3%, significantly lower than 29.0%(P<0.05) in the control, while there was no significant difference respect to the postoperative stone recurrence in the two groups (2.3% vs. 6.5%, P>0.05). Conclusion The primary suture LCBDE is a good choice for patients with choledocholithiasis, which might relieve the postoperative stress reaction and reduce the risk of complications.
Clinical efficacy of LC and ERCP in the treatment of patients with gallbladder and extrahepatic bile duct stones
Liu Songhang, Gao Youkui, Cao Liangqi
2023, 26(1):  132-135.  doi:10.3969/j.issn.1672-5069.2023.01.034
Abstract ( 165 )   PDF (841KB) ( 73 )  
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Objective The aim of this study was to summarize the clinical efficacy of laparoscopic cholecystectomy (LC) and endoscopic retrograde cholangiopancreatography (ERCP) in the treatment of patients with gallbladder and extrahepatic bile duct stones. Methods 142 patients with gallbladder and extrahepatic bile duct stones were encountered in our hospital between March 2018 and March 2022, and 71 patients in control group were treated with traditional open laparotomy, and another 71 patients in observation group were treated with ERCP and thereafter LC. Serum C-reactive protein (CRP) level was detected by immunoturbidimetry, and serum procalcitonin (PCT) level was detected by solid-phase immunochromatography. Serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were assayed by double-antibody one-step sandwich method. Results The surgical time, intraoperative blood loss, the visual analogue scale score and hospital stay in the observation group were (92.3±8.7)min, (47.9±5.2)mL, (3.8±0.4) and (5.2±2.3)d, significantly shorter or less than [(116.4±10.2)min, (76.5±6.4)mL, (4.1±0.5) and (7.1±2.6) d, respectively, P<0.05], while the medical cost was (34000.0±4000.0) yuan, much higher than [(27000.0±3000.0) yuan,P<0.05] in the control; three days after operation, serum CRP, IL-6 and TNF-α levels in the observation were (48.4±2.9)mg/L, (9.7±1.2)ng/L and (1.3±0.2)ng/L, significantly lower than [(61.7±3.1)mg/L, (14.3±1.6)ng/L and (2.4±0.2)ng/L, respectively, P<0.05] in the control; the incidence of post-operationally complications, such as acute pancreatitis, bleeding, infection and bile leak, in the observation was 11.3%, much lower than 23.9%(P<0.05) in the control group. Conclusion The application of ERCP and thereafter LC combination in the treatment of patients with gallbladder and extrahepatic bile duct stones could effectively improve the surgical-related indicators, ensure the stone clearance and promote the postoperative recovery, which might be related to a relatively low systemic inflammatory reactions.
Recurrence three years after liver transplantation of patients with idiopathic portal hypertension: A case report and literature review
Zhang Wei, Hou Wei, Liu Hui, et al
2023, 26(1):  136-139.  doi:10.3969/j.issn.1672-5069.2023.01.035
Abstract ( 144 )   PDF (2860KB) ( 223 )  
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Objective The aim of this study was to report a case of patients with idiopathic portal hypertension(IPH) and review the related literatures. Methods One patients with IPH was reported, and the studies on LT for IPH were retrieved from MEDLINE, EMBASE, Wanfang data and other databases. The outcome after LT in patients with IPH was analyzed. Results A 57-year-old female was clinically diagnosed as liver cirrhosis(LC), underwent LT due to gastrointestinal bleeding and ascites, and the final diagnosis was IPH based on the liver histopathology examination; the percutaneous liver biopsy was performed at the third year of follow-up and showed the nodular regenerative hyperplasia(NRH), with mild portal inflammation and fibrosis, suggesting recurrence of IPH; a total of 81 patients with IHP were retrieved from the literatures, and forty-two patients were diagnosed as LC before LT; the longest follow-up period after LT was 248 months and eight patients died; five patients underwent liver biopsy 3.5 month to 14 years after the first LT, and the pathology showed NRH again; among them, 3 patients developed NRH with portal hypertension after LT in 7th month, 3 years and 14 years, respectively. Conclusions The patients with IPH with severe portal hypertension or liver failure should receive LT, and a few patients might have "recurrence" of IPH, which warrants further investigation.
Serum thyroid hormone levels in patients with nonalcoholic fatty liver disease
Chen Yi,Zhu You,Zhou Xiqiao
2023, 26(1):  145-148.  doi:10.3969/j.issn.1672-5069.2023.01.038
Abstract ( 184 )   PDF (849KB) ( 330 )  
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The nonalcoholic fatty liver disease (NAFLD) is considered to be the metabolic disorders in liver and is closely related to obesity, insulin resistance (IR), type 2 diabetes mellitus (T2DM) and hyperlipemia, etc. The prevalence of NAFLD among adults worldwide is about 25% and it is to believe increasing year by year. The NAFLD is an important causes of liver cirrhosis, liver cancer and liver transplantation. A large number of studies have shown that thyroid hormone (THs) plays an important role in hepatic lipid metabolism and IR, and the thyroid hormone receptor agonists are expected to become new medicines for the treatment of patients with NAFLD. In this review, we mainly discuss the progress of THs in patients with NAFLD.
Impact of hepatic macrophages polarization on pathogenesis of liver cirrhosis
Wu Di, Luo Yehao, Huang An
2023, 26(1):  149-152.  doi:10.3969/j.issn.1672-5069.2023.01.039
Abstract ( 139 )   PDF (845KB) ( 313 )  
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Liver cirrhosis is a very serious chronic progressive liver disease caused by one or more pathological factors repeatedly. The hepatic macrophages is regarded as the important cells for liver damage and repair. The different phenotypic liver macrophages on inflammation of liver are discussed, and the liver macrophage polarization is emphasized in this paper.